The DUX4 protein is a co‐repressor of the progesterone and glucocorticoid nuclear receptors
DUX4 is a transcription factor required during early embryonic development in placental mammals. In this work, we provide evidence that DUX4 is a co‐repressor of nuclear receptors (NRs) of progesterone (PR) and glucocorticoids (GR). The DUX4 C‐ter and N‐ter regions, including the nuclear localizatio...
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| Veröffentlicht in: | FEBS letters 2022-10, Vol.596 (20), p.2644-2658 |
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| creator | Quintero, Julieta Saad, Nizar Y. Pagnoni, Sabrina M. Jacquelin, Daniela K. Gatica, Laura V. Harper, Scott Q. Rosa, Alberto L. |
| description | DUX4 is a transcription factor required during early embryonic development in placental mammals. In this work, we provide evidence that DUX4 is a co‐repressor of nuclear receptors (NRs) of progesterone (PR) and glucocorticoids (GR). The DUX4 C‐ter and N‐ter regions, including the nuclear localization signals and homeodomain motifs, contribute to the co‐repressor activity of DUX4 on PR and GR. Immunoprecipitation studies, using total protein extracts of cells expressing tagged versions of DUX4 and GR, support that these proteins are physically associated. Our studies suggest that DUX4 could modulate gene expression by co‐regulating the activity of hormone NRs. This is the first report highlighting a potential endocrine role for DUX4.
DUX4 is a co‐repressor of the progesterone and glucocorticoid nuclear receptors (NRs). Hormones (H; blue dots) bind their corresponding NRs, activating (+) the expression of a reporter target gene. The activity of the NRs is repressed (−) in the presence of DUX4 (red arrow). Cy, cytoplasm; Nu, nucleus. |
| doi_str_mv | 10.1002/1873-3468.14416 |
| format | Article |
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DUX4 is a co‐repressor of the progesterone and glucocorticoid nuclear receptors (NRs). Hormones (H; blue dots) bind their corresponding NRs, activating (+) the expression of a reporter target gene. The activity of the NRs is repressed (−) in the presence of DUX4 (red arrow). Cy, cytoplasm; Nu, nucleus.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1002/1873-3468.14416</identifier><identifier>PMID: 35662006</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Co-Repressor Proteins ; co‐regulator ; DUX4 ; facioscapulohumeral muscular dystrophy ; Female ; Glucocorticoids ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; hormone nuclear receptor ; Mammals ; Muscular Dystrophy, Facioscapulohumeral - genetics ; Muscular Dystrophy, Facioscapulohumeral - metabolism ; Nuclear Localization Signals ; Placenta - metabolism ; Pregnancy ; Progesterone ; Receptors, Cytoplasmic and Nuclear ; Receptors, Glucocorticoid - genetics ; Transcription Factors</subject><ispartof>FEBS letters, 2022-10, Vol.596 (20), p.2644-2658</ispartof><rights>2022 Federation of European Biochemical Societies.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3446-12fda69b2e575444548956f8e9a11474a2da5f541ab11ac7a205a2a994fbdc0c3</citedby><cites>FETCH-LOGICAL-c3446-12fda69b2e575444548956f8e9a11474a2da5f541ab11ac7a205a2a994fbdc0c3</cites><orcidid>0000-0002-5453-1152 ; 0000-0001-8701-4525</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F1873-3468.14416$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F1873-3468.14416$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35662006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quintero, Julieta</creatorcontrib><creatorcontrib>Saad, Nizar Y.</creatorcontrib><creatorcontrib>Pagnoni, Sabrina M.</creatorcontrib><creatorcontrib>Jacquelin, Daniela K.</creatorcontrib><creatorcontrib>Gatica, Laura V.</creatorcontrib><creatorcontrib>Harper, Scott Q.</creatorcontrib><creatorcontrib>Rosa, Alberto L.</creatorcontrib><title>The DUX4 protein is a co‐repressor of the progesterone and glucocorticoid nuclear receptors</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>DUX4 is a transcription factor required during early embryonic development in placental mammals. In this work, we provide evidence that DUX4 is a co‐repressor of nuclear receptors (NRs) of progesterone (PR) and glucocorticoids (GR). The DUX4 C‐ter and N‐ter regions, including the nuclear localization signals and homeodomain motifs, contribute to the co‐repressor activity of DUX4 on PR and GR. Immunoprecipitation studies, using total protein extracts of cells expressing tagged versions of DUX4 and GR, support that these proteins are physically associated. Our studies suggest that DUX4 could modulate gene expression by co‐regulating the activity of hormone NRs. This is the first report highlighting a potential endocrine role for DUX4.
DUX4 is a co‐repressor of the progesterone and glucocorticoid nuclear receptors (NRs). Hormones (H; blue dots) bind their corresponding NRs, activating (+) the expression of a reporter target gene. The activity of the NRs is repressed (−) in the presence of DUX4 (red arrow). Cy, cytoplasm; Nu, nucleus.</description><subject>Animals</subject><subject>Co-Repressor Proteins</subject><subject>co‐regulator</subject><subject>DUX4</subject><subject>facioscapulohumeral muscular dystrophy</subject><subject>Female</subject><subject>Glucocorticoids</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>hormone nuclear receptor</subject><subject>Mammals</subject><subject>Muscular Dystrophy, Facioscapulohumeral - genetics</subject><subject>Muscular Dystrophy, Facioscapulohumeral - metabolism</subject><subject>Nuclear Localization Signals</subject><subject>Placenta - metabolism</subject><subject>Pregnancy</subject><subject>Progesterone</subject><subject>Receptors, Cytoplasmic and Nuclear</subject><subject>Receptors, Glucocorticoid - genetics</subject><subject>Transcription Factors</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkL1OwzAURi0EoqUwsyGPLGn9n2SE0gJSJZZWYkGW49yUoDQudiLUjUfgGXkSUlq6Ml3dq3M_fToIXVIypISwEU1iHnGhkiEVgqoj1D9cjlGfECoiGae8h85CeCPdntD0FPW4VIoRovroZf4K-G7xLPDauwbKGpcBG2zd9-eXh7WHEJzHrsBNx3XIEkID3tWATZ3jZdVaZ51vSuvKHNetrcB47MHCunE-nKOTwlQBLvZzgBbTyXz8EM2e7h_HN7PIciFURFmRG5VmDGQshRBSJKlURQKpoVTEwrDcyEIKajJKjY0NI9Iwk6aiyHJLLB-g611u1_C97SrqVRksVJWpwbVBMxVzmSacyw4d7VDrXQgeCr325cr4jaZEb53qrUG9Nah_nXYfV_vwNltBfuD_JHaA2gEfZQWb__L0dHLLdsk_90OB3w</recordid><startdate>202210</startdate><enddate>202210</enddate><creator>Quintero, Julieta</creator><creator>Saad, Nizar Y.</creator><creator>Pagnoni, Sabrina M.</creator><creator>Jacquelin, Daniela K.</creator><creator>Gatica, Laura V.</creator><creator>Harper, Scott Q.</creator><creator>Rosa, Alberto L.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5453-1152</orcidid><orcidid>https://orcid.org/0000-0001-8701-4525</orcidid></search><sort><creationdate>202210</creationdate><title>The DUX4 protein is a co‐repressor of the progesterone and glucocorticoid nuclear receptors</title><author>Quintero, Julieta ; Saad, Nizar Y. ; Pagnoni, Sabrina M. ; Jacquelin, Daniela K. ; Gatica, Laura V. ; Harper, Scott Q. ; Rosa, Alberto L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3446-12fda69b2e575444548956f8e9a11474a2da5f541ab11ac7a205a2a994fbdc0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Co-Repressor Proteins</topic><topic>co‐regulator</topic><topic>DUX4</topic><topic>facioscapulohumeral muscular dystrophy</topic><topic>Female</topic><topic>Glucocorticoids</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>hormone nuclear receptor</topic><topic>Mammals</topic><topic>Muscular Dystrophy, Facioscapulohumeral - genetics</topic><topic>Muscular Dystrophy, Facioscapulohumeral - metabolism</topic><topic>Nuclear Localization Signals</topic><topic>Placenta - metabolism</topic><topic>Pregnancy</topic><topic>Progesterone</topic><topic>Receptors, Cytoplasmic and Nuclear</topic><topic>Receptors, Glucocorticoid - genetics</topic><topic>Transcription Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quintero, Julieta</creatorcontrib><creatorcontrib>Saad, Nizar Y.</creatorcontrib><creatorcontrib>Pagnoni, Sabrina M.</creatorcontrib><creatorcontrib>Jacquelin, Daniela K.</creatorcontrib><creatorcontrib>Gatica, Laura V.</creatorcontrib><creatorcontrib>Harper, Scott Q.</creatorcontrib><creatorcontrib>Rosa, Alberto L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quintero, Julieta</au><au>Saad, Nizar Y.</au><au>Pagnoni, Sabrina M.</au><au>Jacquelin, Daniela K.</au><au>Gatica, Laura V.</au><au>Harper, Scott Q.</au><au>Rosa, Alberto L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The DUX4 protein is a co‐repressor of the progesterone and glucocorticoid nuclear receptors</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2022-10</date><risdate>2022</risdate><volume>596</volume><issue>20</issue><spage>2644</spage><epage>2658</epage><pages>2644-2658</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>DUX4 is a transcription factor required during early embryonic development in placental mammals. In this work, we provide evidence that DUX4 is a co‐repressor of nuclear receptors (NRs) of progesterone (PR) and glucocorticoids (GR). The DUX4 C‐ter and N‐ter regions, including the nuclear localization signals and homeodomain motifs, contribute to the co‐repressor activity of DUX4 on PR and GR. Immunoprecipitation studies, using total protein extracts of cells expressing tagged versions of DUX4 and GR, support that these proteins are physically associated. Our studies suggest that DUX4 could modulate gene expression by co‐regulating the activity of hormone NRs. This is the first report highlighting a potential endocrine role for DUX4.
DUX4 is a co‐repressor of the progesterone and glucocorticoid nuclear receptors (NRs). Hormones (H; blue dots) bind their corresponding NRs, activating (+) the expression of a reporter target gene. The activity of the NRs is repressed (−) in the presence of DUX4 (red arrow). Cy, cytoplasm; Nu, nucleus.</abstract><cop>England</cop><pmid>35662006</pmid><doi>10.1002/1873-3468.14416</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-5453-1152</orcidid><orcidid>https://orcid.org/0000-0001-8701-4525</orcidid></addata></record> |
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| subjects | Animals Co-Repressor Proteins co‐regulator DUX4 facioscapulohumeral muscular dystrophy Female Glucocorticoids Homeodomain Proteins - genetics Homeodomain Proteins - metabolism hormone nuclear receptor Mammals Muscular Dystrophy, Facioscapulohumeral - genetics Muscular Dystrophy, Facioscapulohumeral - metabolism Nuclear Localization Signals Placenta - metabolism Pregnancy Progesterone Receptors, Cytoplasmic and Nuclear Receptors, Glucocorticoid - genetics Transcription Factors |
| title | The DUX4 protein is a co‐repressor of the progesterone and glucocorticoid nuclear receptors |
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